Steroidal compounds and method for obtaining the same



Patented ct. 8, 1546 TATES PATENT OFFICE STEROIDAL COMPOUNDS AND METHOD FOR OBTAINING THE SAME No Drawing. Application May 15, 1944, Serial No. 535,749

4 Claims.

This invention relates to the preparation of new compounds of the pregnane series Which are CH S Oxidation l Hydrolysis where S represents the rings A, B and C of the steroid nucleus and R is an acyl radical (R20 representing an acyl anhydride).

I have now found that these reactions may also be applied to newly discovered steroidal sapogenins which are oxygenated in Ring C at position 12, e. g. hecogenin (l2-ketotigogenin), rockogenin (l2-hydroxy-tigogenin) and furcogenin (12-hydroxy-smilagenin). The corresponding pseudo-sapogenins are described in my co- 2 pending application Serial No. 535,757, filed May 15, 1944. Rockogenin is described in my copending application Serial No. 535,758, filed May 15, 1944. See J. Am. Chem. Soc. 65, 1199 (1943).

The invention may be illustrated by the following example:

Pseud0hecogem'n.A sealed tube containing 5 g. of hecogenin and 15 cc. of acetic anhydride was heated at 200 for 10 hours. The solvent was removed in vacuo and the solid residue was treated with a solution of 5 g. of potassium hydroxide in 500 cc. ethanol for thirty minutes. The product was ether extracted and the ethereal solution was washed and evaporated. The acetone solution of the residue after treatment with Norite wa concentrated and cooled to give white needles, M. P. 189191; yield 2.6 g.

AnaL: Calcd for 0271-14204: C, 75.3; H, 9.8. Found: C, 75.2; H, 9.9.

16-aZZO-qoregnen-3,12,20-trione.-To a solution' of 1 g. of pseudohecogenin in 40 cc. of acetic acid at 15 was added 0.9 g. of chromic anhydride dissolved in 10 cc. acetic acid. A dark brown solid precipitated. Within twenty minutes this solid material dissolved. The mixture was allowed to stand at 25 a total of minutes with frequent shaking. The product was extracted with ether and the ethereal solution was washed thoroughly with water to remove the acetic acid. The ether was removed and the solid residue was treated with cc. of a 2% alcoholic Potassium hydroxide solution for thirty minutes. The mixture was cooled andether extracted. After washing and concentrating, the ethereal solution was cooled to give fine white plates, M. P. 256-258; yield mg.

Anal: Calcd for C21H2303.H201 C, 72.8; H, 8.7. Found: C, 72.6, H, 8.8.

AlZo-pregnen-3,12,20-tri0ne.A solution of 50 mg. of 16-allo-pregnen-3,12,20-trione in 300 cc. of ether was shaken with hydrogen and one gram 3% palladium-barium sulphate catalyst at room temperature and 3 atm. for two hours. The mixture was filtered through kieselguhr and the filtrate was concentrated to give white crystals,

3 M. P. mil-264. This material was insoluble in both hot and cold aqueous potassium hydroxide.

Anal: Calod for C21H3oO3l-I20: C, 72.4; H, 9.3. Found: C, 72.9; H, 9.1.

The example given is for the purpose of illustrating the invention and can be varied considerably for the purpose of obtaining different pregnane compounds. For example, if pseudohecogenindiacetate be oxidized directly with subsequent hydrolysis the product of the reacl0 ides, acetyl chloride, benzoyl chloride, furoyl tion sequence will be 3-o-hydroxy-12, ZO-diketochloride, butyric or other lower fatty acid anhyl6-al10-pregnene. In the same manner if pseudodride, etc. One can form an alkali metal alcorockogenin-tri-acetate be oxidized with subseholate of the sapogenin hydroxy compound and quent hydrolysis the end product is 3,12-dihythen react it with an alkyl halide to form an droxy-20-keto-16-al1o-pregnene. Oxidation of 15 ether. One can also react the hydroxyl containpseudo-rookogenin followed by hydrolysis yields ing sapogenin with a compound such as tri- 3,12,20-t1fiet0 -a 0-D e Processing of phenyl methyl chloride to form the so-called pseudo-furcogenin diaoetate similarly yields 3- trityl ether type. Halogenating agents, such as hydroxy-12-20-di-keto-lfi-pregnene while oxidasulfuryl chloride, phosphorus chlorides and the tion of the free genin yields as final product 20 like may also be usedto convert OH to halogen. 3,12,20-tri-keto-pregnene. The hydroxylated The main transformations occurring in the pregnenes obtained in t manner ay be eabove examples startin with hecogenin, rockoacylated to obtain ester derivatives for example genin and furcogenin may be represented as folby boiling with acetic anhydride. lows:

While the oxidizing agent described, chromic 25 Starting with hecogenin:

0 CH3 CH2 CH2 cm H CH3 oH-o CH-CH; l\ H O-CH2 o D b B H0 Hecogenin Rzolandheat on OH OH CH CH3 6 CH3 1 3 2 OH: CE; a

V 0 CH-OH: c=o oH-OH. H 011,01: (\H CHT-OH I Hydrolysis I I/\ /Y \/\H p /Y \/\H R0 HO Pseudohecogenin diacylate Pseudohecogenin oxidation 1 and hydrolysis oxidationl and hydrolysis OH CH CH3 CH3 CH; on: a

.0 l l ,l I

3-B-hydroxy-l2,20-diketolfi-allo-pregnenelfi-allo-pregnene 3,12,20-trione 2,408,828 a 8 where Y and Y are members of the class "7 What I claim is: 1. A compound represented by the following formula:

Y! OH; I H v E=o 5 groups hydrolyzable to H \/\H 10 and =0.

2. 16-A110-pregnene-3,12,20-trione. 3. l6-Pregnene-3-ol-'12,20-d1one.

4. 16-A11o-pregnene-3,12-dio1-20-one.

ROMEO B. WAGNER. 

